1. Epidemiology and Global Health

A sex-specific Mendelian randomization-phenome-wide association study of body mass index

  1. Zhu Liduzi Jiesisibieke
  2. Io Ieong Chan
  3. Jack Chun Man Ng
  4. C Mary Schooling  Is a corresponding author
  1. School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, China
  2. Department of Public Health and Medicinal Administration, Faculty of Health Sciences, University of Macau, China
  3. Graduate School of Public Health and Health Policy, City University of New York, United States
https://doi.org/10.7554/eLife.102573.3
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  1. Zhu Liduzi Jiesisibieke
  2. Io Ieong Chan
  3. Jack Chun Man Ng
  4. C Mary Schooling
(2025)
A sex-specific Mendelian randomization-phenome-wide association study of body mass index
eLife 13:RP102573.
https://doi.org/10.7554/eLife.102573.3
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3 figures, 1 table and 2 additional files

Figures

Figure 1
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Selection criteria for the phenotypes.
Figure 2
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Manhattan plot of body mass index on phenotypes in men (n: 167,020) from the UK Biobank.

Note: The dotted lines indicate the significant threshold.

Figure 3
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Manhattan plot of body mass index on phenotypes in women (n: 194,174) from the UK Biobank.

Note: The dotted lines indicate the significant threshold.

Tables

Table 1
Sex differences of body mass index on phenotypes in men (n: 167,020) and women (n: 194,174).

Red: Stronger associations in women and different directions in men and women; Green: Stronger associations in men and different directions in men and women; Orange: Stronger associations in women and same directions in men and women; Blue: Stronger associations in men and same directions in men and women.

CategoryPhenotypesMenWomenSex difference after false-discovery rate
Blood assaysSHBG↓↓√
Albumin↓↓×
Vitamin D↓↓√
Cholesterol↓↓×
Total bilirubin↓↓×
LDL cholesterol↓↓√
Direct bilirubin↓↓√
Platelet count↓↑×
Testosterone↓↑√
Apoliprotein B↓↑√
Platelet crit↓↑√
Aspartate aminotransferase↑↑×
Alkaline phosphatase↑↑×
Neutrophill count↑↑×
Red blood cell (erythrocyte) distribution width↑↑×
Triglycerides↑↑×
Urate↑↑√
C-reactive protein↑↑√
Diseases of the circulatory systemDiagnoses – main ICD10: I35 Nonrheumatic aortic valve disorders↑↑×
Peripheral artery disease↑↑√
Death due to cardiac causes↑↑×
Heart failure, strict↑↑×
Diagnoses – main ICD10: I26 Pulmonary embolism↑↑×
DVT of lower extremities and pulmonary embolism↑↑×
Venous thromboembolism↑↑×
Myocardial infarction, strict↑↑√
Major coronary heart disease event↑↑√
Major coronary heart disease event excluding revascularizations↑↑√
Coronary atherosclerosis↑↑√
Ischemic heart disease, wide definition↑↑√
Diseases of the circulatory system↑↑×
Diseases of the digestive systemDiagnoses – main ICD10: K60 Fissure and fistula of anal and rectal regions↑↑×
Diagnoses – main ICD10: K81 Cholecystitis↑↑×
Hernia↓↑√
Diagnoses – main ICD10: K80 Cholelithiasis↑↑√
Disorders of gallbladder, biliary tract, and pancreas↑↑√
Diseases of the digestive system↑↑√
Diseases of the genitourinary systemDiagnoses – main ICD10: N17 Acute renal failure↑↑×
Diagnoses – main ICD10: N39 Other disorders of urinary system↑↑√
Diseases of the hematopoietic system and blood disordersOther anemias↓↑×
Other and unspecified anemias↓↑×
Iron deficiency anemia↓↑√
Diseases of the blood and blood-forming organs and certain disorders involving the immune mechanism↑↑√
Diseases of the musculoskeletal system and connective tissueCervicalgia↓↑×
Soft tissue disorders related to use, overuse, and pressure↑↑×
Impingement syndrome of shoulder↑↑×
Pain in limb↑↑√
Other soft tissue disorders, not elsewhere classified↑↑√
Diagnoses – main ICD10: M79 Other soft tissue disorders, not elsewhere classified↑↑√
Diseases of the nervous systemDiagnoses – main ICD10: G57 Mononeuropathies of lower limb↓↑×
Sleep apnea↑↑×
Diagnoses – main ICD10: G47 Sleep disorders↑↑×
Carpal tunnel syndrome↑↑×
Nerve, nerve root, and plexus disorders↑↑×
Diseases of the respiratory systemDiagnoses – main ICD10: J18 Pneumonia, organism unspecified↑↑√
Diseases of the respiratory system↑↑×
Diseases of the sensory systemDiagnoses – main ICD10: H61 Other disorders of external ear↑↓×
Degeneration of macula and posterior pole↓↑×
Diseases of the skin and subcutaneous tissueDiagnoses – main ICD10: L03 Cellulitis↑↑√
Endocrine and metabolic diseasesDiabetes diagnosed by doctor↑↑√
Health and medical historyBlood clot, DVT, bronchitis, emphysema, asthma, rhinitis, eczema, allergy diagnosed by doctor: hay fever, allergic rhinitis, or eczema↓↓√
Blood clot, DVT, bronchitis, emphysema, asthma, rhinitis, eczema, allergy diagnosed by doctor: none of the above↑↓√
Vascular/heart problems diagnosed by doctor: heart attack↑↑√
Chest pain or discomfort↑↑×
Mouth/teeth dental problems: dentures↑↑×
Lifestyle and environmentalMorning/evening person (chronotype)↓↓×
Facial aging↑↑√
Medical conditionsNon-cancer illness code, self-reported: osteoporosis↓↓×
Non-cancer illness code, self-reported: headaches (not migraine)↓↑×
Non-cancer illness code, self-reported: pernicious anemia↓↑×
Non-cancer illness code, self-reported: psoriatic arthropathy↓↑×
Non-cancer illness code, self-reported: eye/eyelid problem↓↑×
Non-cancer illness code, self-reported: allergy/hypersensitivity/anaphylaxis↓↑×
Non-cancer illness code, self-reported: ulcerative colitis↑↓×
Non-cancer illness code, self-reported: bladder problem (not cancer)↓↑×
Non-cancer illness code, self-reported: Helicobacter pylori↑↑×
Non-cancer illness code, self-reported: muscle or soft tissue injuries↑↓√
Non-cancer illness code, self-reported: muscle/soft tissue problem↓↑×
Non-cancer illness code, self-reported: gout↑↑√
Non-cancer illness code, self-reported: cervical spondylosis↑↑×
Non-cancer illness code, self-reported: arthritis (nos)↑↑×
Non-cancer illness code, self-reported: unclassifiable↓↑×
Non-cancer illness code, self-reported: cholelithiasis/gall stones↑↑√
Non-cancer illness code, self-reported: depression↑↑×
Non-cancer illness code, self-reported: hypothyroidism/myxoedema↑↑√
Non-cancer illness code, self-reported: gastro-esophageal reflux (gord) / gastric reflux↑↑×
Non-cancer illness code, self-reported: angina↑↑√
Non-cancer illness code, self-reported: asthma↑↑√
Non-cancer illness code, self-reported: osteoarthritis↑↑×
NeoplasmsMalignant neoplasm of urinary organs↑↓×
Diagnoses – main ICD10: D35 Benign neoplasm of other and unspecified endocrine glands↑↑×
Malignant neoplasm of colon↑↓×
Lymphomas↑↑×
Malignant neoplasm of digestive organs↑↑×
Physical measuresHand grip strength (right)↑↓×
Diastolic blood pressure, automated reading↑↑√
Physiological factorsSensitivity/hurt feelings↓↑√
Neuroticism score↓↑×
Seen doctor (GP) for nerves, anxiety, tension, or depression↓↑√
Miserableness↑↑√
Loneliness, isolation↑↑√
Fed-up feelings↑↑√
SymptomsDiagnoses – main ICD10: R04 Hemorrhage from respiratory passages↑↓√
Diagnoses – main ICD10: R31 Unspecified hematuria↑↓√
Urine assaysPotassium in urine↑↑×

Additional files

Supplementary file 1

Sex-specific UK Biobank phewas estimates (a), counts of significant associations (b), and MR-Egger estimates (c).

(a) Phenome-wide association analysis of causal estimates for body mass index from the UK Biobank (women: 194,174; men: 167,020) and sex-specific and sex-combined Genetic Investigation of ANthropometric Traits (GIANT) (sex-specific: women: 171,977, men: 152,893; sex-combined: 681,275) on attributes (women: 194,174; men: 167,020) from the UK Biobank based on inverse variance weighting. (b) Number of significant associations of body mass index from UK Biobank (women: 194,174; men: 167,020) and sex-specific and sex-combined GIANT (sex-specific: women: 171,977, men: 152,893; sex-combined: 681,275) with phenotypes from UK Biobank (women: 194,174; men: 167,020) by category. (c) MR-Egger sensitivity analysis of phenome-wide association causal estimates for body mass index on various phenotypes in women (n: 194,174) and men (n: 167,020) from the UK Biobank. Abbreviations used in supplementary files: Irnt: inverse rank normalized; SHBG: sex hormone binding globulin; GIANT: Genetic Investigation of ANthropometric Traits; GV: genetic variant; GWAS: genome-wide association study; ICD: International Classification of Diseases.

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  1. Zhu Liduzi Jiesisibieke
  2. Io Ieong Chan
  3. Jack Chun Man Ng
  4. C Mary Schooling
(2025)
A sex-specific Mendelian randomization-phenome-wide association study of body mass index
eLife 13:RP102573.
https://doi.org/10.7554/eLife.102573.3